Host pigments: potential facilitators of photosynthesis in coral symbioses

Reef‐building corals occur as a range of colour morphs because of varying types and concentrations of pigments within the host tissues, but little is known about their physiological or ecological significance. Here, we examined whether specific host pigments act as an alternative mechanism for photoacclimation in the coral holobiont. We used the coral Montipora monasteriata (Forskål 1775) as a case study because it occurs in multiple colour morphs (tan, blue, brown, green and red) within varying light‐habitat distributions. We demonstrated that two of the non‐fluorescent host pigments are responsive to changes in external irradiance, with some host pigments up‐regulating in response to elevated irradiance. This appeared to facilitate the retention of antennal chlorophyll by endosymbionts and hence, photosynthetic capacity. Specifically, net P_max Chl a^?1 correlated strongly with the concentration of an orange‐absorbing non‐fluorescent pigment (CP‐580). This had major implications for the energetics of bleached blue‐pigmented (CP‐580) colonies that maintained net P_max cm^?2 by increasing P_max Chl a^?1. The data suggested that blue morphs can bleach, decreasing their symbiont populations by an order of magnitude without compromising symbiont or coral health.     

Immuno-proteomic approach to excitation--contraction coupling in skeletal and cardiac muscle: molecular insights revealed by the mitsugumins

A comprehensive understanding of excitation-contraction (E-C) coupling in skeletal and cardiac muscle requires that all the major components of the Ca(2+) release machinery be resolved. We utilized a unique immuno-proteomic approach to generate a monoclonal antibody library that targets proteins localized to the skeletal muscle triad junction, which provides a structural context to allow efficient E-C coupling. Screening of this library has identified several mitsugumins (MG); proteins that can be localized to the triad junction in mammalian skeletal muscle. Many of these proteins, including MG29 and junctophilin, are important components in maintaining the structural integrity of the triad junction. Other triad proteins, such as calumin, play a more direct role in regulation of muscle Ca(2+) homeostasis. We have recently identified a family of trimeric intracellular cation-selective (TRIC) channels that allow for K(+) movement into the endoplasmic or sarcoplasmic reticulum to counter a portion of the transient negative charge produced by Ca(2+) release into the cytosol. Further study of TRIC channel function and other novel mitsugumins will increase our understanding of E-C coupling and Ca(2+) homoeostasis in muscle physiology and pathophysiology.     

Abiotic nitrate incorporation, anaerobic microsites, and the ferrous wheel

Nitrate has long been thought to be chemically unreactive in soil. This view was challenged by the report of an apparently abiotic process whereby nitrate (NO₃ ^?) is incorporated into organic compounds (Dail et al. 2001). In Colman et al. (2007), we examined how common this process might be by testing for it in 45 soils collected from across a range of ecosystem types. We found no evidence of this process occurring in any of the soils, but found evidence of an analytical artifact that creates the appearance of incorporation. We suggested that prior evidence of this process might be due in part or in total to this analytical artifact. Davidson et al. (2008), however, challenged our results and conclusions, suggesting that we failed to observe the abiotic incorporation because we eliminated the anaerobic microsites they argue are necessary for the process. We address the criticisms, and show that they actually raise questions about the robustness of the only study to have reported abiotic NO₃ ^? incorporation in sterile soils. We argue that this area of research needs new artifact-free experiments if the controversy is going to be resolved.     

Synthesis and structure-activity relationships of heteroaryl substituted-3,4-diamino-3-cyclobut-3-ene-1,2-dione CXCR2/CXCR1 receptor antagonists

Comprehensive SAR studies were undertaken in the 3,4-diaminocyclobut-3-ene-1,2-dione class of CXCR2/CXCR1 receptor antagonists to explore the role of the heterocycle on chemokine receptor binding affinities, functional activity, as well as oral exposure in rat. The nature of the heterocycle as well as the requisite substitution pattern around the heterocycle was shown to have a dramatic effect on the overall biological profile of this class of compounds. The furyl class, particularly the 4-halo adducts, was found to possess superior binding affinities for both the CXCR2 and CXCR1 receptors, functional activity, as well as oral exposure in rat versus other heterocyclic derivatives.     

Differential CMV-specific CD8+ effector T cell responses in the lung allograft predominate over the blood during human primary infection

Acquisition of T cell responses during primary CMV infection in lung transplant recipients (LTRs) appear critical for host defense and allograft durability, with increased mortality in donor+/recipient- (D+R-) individuals. In 15 D+R- LTRs studied, acute primary CMV infection was characterized by viremia in the presence or absence of pneumonitis, with viral loads higher in the lung airways/allograft compared with the blood. A striking influx of CD8+ T cells into the lung airways/allograft was observed, with inversion of the CD4+:CD8+ T cell ratio. De novo CMV-specific CD8+ effector frequencies in response to pooled peptides of pp65 were strikingly higher in lung mononuclear cells compared with the PBMC and predominated over IE1-specific responses and CD4+ effector responses in both compartments. The frequencies of pp65-specific cytokine responses were significantly higher in lung mononuclear cells compared with PBMC and demonstrated marked contraction with long-term persistence of effector memory CD8+ T cells in the lung airways following primary infection. CMV-tetramer+CD8+ T cells from PBMC were CD45RA- during viremia and transitioned to CD45RA+ following resolution. In contrast, CMV-specific CD8+ effectors in the lung airways/allograft maintained a CD45RA- phenotype during transition from acute into chronic infection. Together, these data reveal differential CMV-specific CD8+ effector frequencies, immunodominance, and polyfunctional cytokine responses predominating in the lung airways/allograft compared with the blood during acute primary infection. Moreover, we show intercompartmental phenotypic differences in CMV-specific memory responses during the transition to chronic infection.     

Patterns of parasite abundance and distribution in island populations of Galápagos endemic birds

Parasite life-history characteristics, the environment, and host defenses determine variation in parasite population parameters across space and time. Parasite abundance and distribution have received little attention despite their pervasive effects on host populations and community dynamics. We used analyses of variance to estimate the variability of intensity, prevalence, and abundance of 4 species of lice (Insecta: Phthiraptera) infecting Galápagos doves and Galápagos hawks and 1 haemosporidian parasite (Haemosporida: Haemoproteidae) infecting the doves across island populations throughout their entire geographic ranges. Population parameters of parasites with direct life cycles varied less within than among parasite species, and intensity and abundance did not differ significantly across islands. Prevalence explained a proportion of the variance (34%), similar to infection intensity (33%) and parasite abundance (37%). We detected a strong parasite species-by-island interaction, suggesting that parasite population dynamics is independent among islands. Prevalence (up to 100%) and infection intensity (parasitemias up to 12.7%) of Haemoproteus sp. parasites varied little across island populations.     

Calcium stores in hippocampal synaptic boutons mediate short-term plasticity, store-operated Ca2+ entry, and spontaneous transmitter release

Evoked transmitter release depends upon calcium influx into synaptic boutons, but mechanisms regulating bouton calcium levels and spontaneous transmitter release are obscure. To understand these processes better, we monitored calcium transients in axons and presynaptic terminals of pyramidal neurons in hippocampal slice cultures. Action potentials reliably evoke calcium transients in axons and boutons. Calcium-induced calcium release (CICR) from internal stores contributes to the transients in boutons and to paired-pulse facilitation of EPSPs. Store depletion activates store-operated calcium channels, influencing the frequency of spontaneous transmitter release. Boutons display spontaneous Ca2+ transients; blocking CICR reduces the frequency of these transients and of spontaneous miniature synaptic events. Thus, spontaneous transmitter release is largely calcium mediated, driven by Ca2+ release from internal stores. Bouton store release is important for short-term synaptic plasticity and may also contribute to long-term plasticity.     

Nonspecific adherence by Actinobacillus actinomycetemcomitans requires genes widespread in bacteria and archaea

The gram-negative coccobacillus, Actinobacillus actinomycetemcomitans, is the putative agent for localized juvenile periodontitis, a particularly destructive form of periodontal disease in adolescents. This bacterium has also been isolated from a variety of other infections, notably endocarditis. Fresh clinical isolates of A. actinomycetemcomitans form tenacious biofilms, a property likely to be critical for colonization of teeth and other surfaces. Here we report the identification of a locus of seven genes required for nonspecific adherence of A. actinomycetemcomitans to surfaces. The recently developed transposon IS903phikan was used to isolate mutants of the rough clinical isolate CU1000 that are defective in tight adherence to surfaces (Tad(-)). Unlike wild-type cells, Tad(-) mutant cells adhere poorly to surfaces, fail to form large autoaggregates, and lack long, bundled fibrils. Nucleotide sequencing and genetic complementation analysis revealed a 6.7-kb region of the genome with seven adjacent genes (tadABCDEFG) required for tight adherence. The predicted TadA polypeptide is similar to VirB11, an ATPase involved in macromolecular transport. The predicted amino acid sequences of the other Tad polypeptides indicate membrane localization but no obvious functions. We suggest that the tad genes are involved in secretion of factors required for tight adherence of A. actinomycetemcomitans. Remarkably, complete and highly conserved tad gene clusters are present in the genomes of the bubonic plague bacillus Yersinia pestis and the human and animal pathogen Pasteurella multocida. Partial tad loci also occur in strikingly diverse Bacteria and Archaea. Our results show that the tad genes are required for tight adherence of A. actinomycetemcomitans to surfaces and are therefore likely to be essential for colonization and pathogenesis. The occurrence of similar genes in a wide array of microorganisms indicates that they have important functions. We propose that tad-like genes have a significant role in microbial colonization.     

Neuronal fractalkine expression in HIV-1 encephalitis: roles for macrophage recruitment and neuroprotection in the central nervous system

HIV-1 infection of the brain results in chronic inflammation, contributing to the neuropathogenesis of HIV-1 associated neurologic disease. HIV-1-infected mononuclear phagocytes (MP) present in inflammatory infiltrates produce neurotoxins that mediate inflammation, dysfunction, and neuronal apoptosis. Neurologic disease is correlated with the relative number of MP in and around inflammatory infiltrates and not viral burden. It is unclear whether these cells also play a neuroprotective role. We show that the chemokine, fractalkine (FKN), is markedly up-regulated in neurons and neuropil in brain tissue from pediatric patients with HIV-1 encephalitis (HIVE) compared with those without HIVE, or that were HIV-1 seronegative. FKN receptors are expressed on both neurons and microglia in patients with HIVE. These receptors are localized to cytoplasmic structures which are characterized by a vesicular appearance in neurons which may be in cell-to-cell contact with MPs. FKN colocalizes with glutamate in these neurons. Similar findings are observed in brain tissue from an adult patient with HIVE. FKN is able to potently induce the migration of primary human monocytes across an endothelial cell/primary human fetal astrocyte trans-well bilayer, and is neuroprotective to cultured neurons when coadministered with either the HIV-1 neurotoxin platelet activating factor (PAF) or the regulatory HIV-1 gene product Tat. Thus focal inflammation in brain tissue with HIVE may up-regulate neuronal FKN levels, which in turn may be a neuroimmune modulator recruiting peripheral macrophages into the brain, and in a paracrine fashion protecting glutamatergic neurons.